Method of making



Donald M. Burness, Rochester, N; YL, assignor to Eastman Kodak Company, Rochester, N; :Y., a corporation of New Jersey No Drawing. Application May 26, 1953, Serial No. 357,645

3 Claims. (Cl. 260-594) This invention relates to the preparation of fl-ketoacetals and is particularly concerned with a new method of making a dialkyl acetal of B-ketobutyraldehyde.

The fi-ketoacetals are useful intermediates in the synthesis of a,,8-unsaturated aldehydes, and the dialkyl acetals of fi-ketobutyraldehyde are particularly useful in the synthesis of vitamin A compounds, sulfamerazine and similar pharmaceuticals.

It is an object of this invention to provide a new method of making B-ketoacetals without the disadvantages attendant to processes employing ,B-chlorovinyl ketones. I

It is a further object of this invention to provide a new and convenient method of preparing B-ketoacetals employing stable and readily prepared intermediates.

Another object of the invention is to provide a method adapted for large-scale production of fi-ketoacetals in good yield.

Another object of the invention is to facilitate the synthesis of vitamin A by making available in commercial quantities a useful intermediate in vitamin A syntheses.

Another object of the invention is to provide a hitherto unknown and effective method of making dialkyl acetals of fi-ketobutyraldehyde.

Other objects will be apparent from the description and claims which follow.

These and other objects of the invention are attained by the process comprising reacting an alkali metal formyl acetone such as sodium formyl acetone (also sometimes called sodium hydroxy methylene acetone) with an alkyl halide and an alkyl alcohol and thereby forming a dialkyl acetal of fi-ketobutyraldehyde. In a preferred embodiment of the invention, the alkali metal formyl acetone is prepared by reacting an alkali metal with an alkyl formate, such as methyl or ethyl formate, and acetone, separating the resulting salt from the reaction mixture, and reacting the salt with an alkyl halide in a solution of the corresponding alkyl alcohol and in the presence of an alkali metal iodide.

The alkali metal formyl acetone compounds are readily prepared and form stable intermediates particularly adapted for commercial production of the desired B-ketoacetals. A preferred method of preparing the alkali metal salt is illustrated by the following equation wherein the alkali metal is sodium, it being understood that potassium or lithium or an alkali metal alkoxide such as sodium methoxide can be used instead of the preferred sodium metal if desired.

example at l0 C. The alkali metal formyl acetone is then separated from the reaction mixture to free it of unreacted sodium, sodium alkoxides or the like which nited States Patent 0 "Ice , catal yze undesired side reactions in; the subsequent! steps-.

well-known alkyl halides can" bev employed. with the bromides being preferred to: thesl'es'srsuitable chlorides,-

iodides. and fluorides; Similarly any of the: well-known alkyl alcohols;- can: be: employed, and in the preferred embodiment, the: alkyl! alcohol corresponds to: the. alkyl. hal? ide. Thus, for example, methyl. alcohol. i'sdesirably ems ployed with a methyl halide; ethyl alcohol with an et-hyl halide, etc. The alkyl group can be any alkyl group depending upon the particular acetal desired; although, for convenience, the lower alkyl halides and alcohols are preferred, such as the methyl, ethyl, propyl and butyl halides and alcohols. The reaction is desirably carried out in a solution of the absolute alkyl alcohol, no other solvent being necessary. The reaction is illustrated by the following equation typifying the preparation of a diethyl acetal:

N81 CH3COCH=CHON8 CzHsBr CzHsOH CHaCOCHaCH(O GrHs) Equation II The invention is illustrated by the following examples of a preferred embodiment, it being understood that the reactants can be varied as described hereinabove.

Example 1 A mixture of 48 g. of powdered sodium'metal in 500 mlof dry ether was placedin a 2-liter 3-necked flask, and cooled in an ice-salt bath. The mixture was stirred and maintained at a temperature of 0-10 C. while a mixture of 200 g. of ethyl formate and 120 g. of acetone was added dropwise over a period of 1.5 hours. The resulting reaction mixture was allowed to stand overnight, then' Example 2 A mixture of 200 g. of the dry sodium formyl acetone, 1000 ml. of absolute ethanol, 370 g. of ethyl bromide, and 1 g. of sodium iodide was stirred at room temperature and under anhydrous conditions for 88 hours. An additional 100 g. portion of ethyl bromide was added, and the reaction mixture was heated under reflux for an additional 8 hours. Solids were removed from the reaction mixture by filtration, and residual alcohol was removed from the filtrate by vacuum evaporation. The weakly alkaline residual oil thus obtained was dried over anhydrous magnesium sulfate, filtered again, stabilized with a trace of hydroquinone and distilled. The fraction boiling in the range of from 62 C. at 6 mm. pressure to C. at 8 mm. pressure was collected and weighed 122 g. The product was then dried over anhydrous magnesium sulfate and, redistilled through a 6-inch Vigreux column to give 101 g. of colorless liquid having B. R: 6668 C. at 8 mm. and n =l.4268. The analysis showed C=6l.2 and H=l0.2 as compared to the calculated C=60.0 and H=l0.1 for CsHmOa. Infra-red analysis showed the product to be predominantly the diethyl acetal of ,B-ketobutyraldehyde.

The invention thus provides an effective method of making dialkyl acetals of ,B-ketobutyraldehyde from stable and readily prepared intermediates.

Whilethe invention has been described in considerable detail with reference to certain preferred embodiments thereof, it will be understood that variations and modifications can be effected within the spirit and scope of the invention as described hereinabove and as defined in the appended claims.

I claim:

l. The method of making a dialkyl acetal of p-ketobutyraldehyde which comprises reacting an alkali metal formyl acetone, an alkyl halide, and an alkyl alcohol in the presence of an alkali metal iodide.

2. The method of making a dialkyl acetal of fii-ketobutyraldehyde which comprises reacting sodium formyl acetone with an alkyl halide and an alkyl alcohol in the 7 presence of sodium iodide.

3. The method of making a dialkyl acetal of fi-ketobutyraldehyde which comprises reacting an alkali metal formyl acetone with an alkyl bromide and an alkyl alcohol in the presence of an alkali metal iodide.

References Cited in the file of this patent UNITED STATES PATENTS Bordenca et' al Oct. 8, 1946 Richmond .c Oct. 9, 1951 

1. THE METHOD OF MAKING A DIALKYL ACETAL OF B-KETOBUTYRALDEHYDE WHICH COMPRISES REACTING AN ALKALI METAL FORMYL ACETONE, AN ALKYL HALIDE, AND AN ALKYL ALCOHOL IN THE PRESENCE OF AN ALKALI METAL IODIDE. 